Research ExplorerPublicationsA vaccine targeting mutant IDH1 induces antitumour immunity

A vaccine targeting mutant IDH1 induces antitumour immunity

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A vaccine targeting mutant IDH1 induces antitumour immunity. / Schumacher, Theresa; Bunse, Lukas; Pusch, Stefan; Sahm, Felix; Wiestler, Benedikt; Quandt, Jasmin; Menn, Oliver; Osswald, Matthias; Oezen, Iris; Ott, Martina; Keil, Melanie; Balß, Jörg; Rauschenbach, Katharina; Grabowska, Agnieszka K; Vogler, Isabel; Diekmann, Jan; Trautwein, Nico; Eichmüller, Stefan B; Okun, Jürgen; Stevanović, Stefan; Riemer, Angelika B; Sahin, Ugur; Friese, Manuel A; Beckhove, Philipp; von Deimling, Andreas; Wick, Wolfgang; Platten, Michael.

In: NATURE, Vol. 512, No. 7514, 21.08.2014, p. 324-7.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Schumacher, T, Bunse, L, Pusch, S, Sahm, F, Wiestler, B, Quandt, J, Menn, O, Osswald, M, Oezen, I, Ott, M, Keil, M, Balß, J, Rauschenbach, K, Grabowska, AK, Vogler, I, Diekmann, J, Trautwein, N, Eichmüller, SB, Okun, J, Stevanović, S, Riemer, AB, Sahin, U, Friese, MA, Beckhove, P, von Deimling, A, Wick, W & Platten, M 2014, 'A vaccine targeting mutant IDH1 induces antitumour immunity', NATURE, vol. 512, no. 7514, pp. 324-7. https://doi.org/10.1038/nature13387

APA

Schumacher, T., Bunse, L., Pusch, S., Sahm, F., Wiestler, B., Quandt, J., Menn, O., Osswald, M., Oezen, I., Ott, M., Keil, M., Balß, J., Rauschenbach, K., Grabowska, A. K., Vogler, I., Diekmann, J., Trautwein, N., Eichmüller, S. B., Okun, J., ... Platten, M. (2014). A vaccine targeting mutant IDH1 induces antitumour immunity. NATURE, 512(7514), 324-7. https://doi.org/10.1038/nature13387

Vancouver

Schumacher T, Bunse L, Pusch S, Sahm F, Wiestler B, Quandt J et al. A vaccine targeting mutant IDH1 induces antitumour immunity. NATURE. 2014 Aug 21;512(7514):324-7. https://doi.org/10.1038/nature13387

Bibtex

@article{a93a9c0639b54d61bd74d8b1cbef384c,
title = "A vaccine targeting mutant IDH1 induces antitumour immunity",
abstract = "Monoallelic point mutations of isocitrate dehydrogenase type 1 (IDH1) are an early and defining event in the development of a subgroup of gliomas and other types of tumour. They almost uniformly occur in the critical arginine residue (Arg 132) in the catalytic pocket, resulting in a neomorphic enzymatic function, production of the oncometabolite 2-hydroxyglutarate (2-HG), genomic hypermethylation, genetic instability and malignant transformation. More than 70% of diffuse grade II and grade III gliomas carry the most frequent mutation, IDH1(R132H) (ref. 3). From an immunological perspective, IDH1(R132H) represents a potential target for immunotherapy as it is a tumour-specific potential neoantigen with high uniformity and penetrance expressed in all tumour cells. Here we demonstrate that IDH1(R132H) contains an immunogenic epitope suitable for mutation-specific vaccination. Peptides encompassing the mutated region are presented on major histocompatibility complexes (MHC) class II and induce mutation-specific CD4(+) T-helper-1 (TH1) responses. CD4(+) TH1 cells and antibodies spontaneously occurring in patients with IDH1(R132H)-mutated gliomas specifically recognize IDH1(R132H). Peptide vaccination of mice devoid of mouse MHC and transgenic for human MHC class I and II with IDH1(R132H) p123-142 results in an effective MHC class II-restricted mutation-specific antitumour immune response and control of pre-established syngeneic IDH1(R132H)-expressing tumours in a CD4(+) T-cell-dependent manner. As IDH1(R132H) is present in all tumour cells of these slow-growing gliomas, a mutation-specific anti-IDH1(R132H) vaccine may represent a viable novel therapeutic strategy for IDH1(R132H)-mutated tumours.",
keywords = "Animals, Antibody Specificity, Antigens, Neoplasm, Cancer Vaccines, Female, Glioma, Histocompatibility Antigens Class II, Humans, Immunity, Humoral, Immunotherapy, Isocitrate Dehydrogenase, Male, Mice, Mutant Proteins, Mutation, T-Lymphocytes, Helper-Inducer, Xenograft Model Antitumor Assays",
author = "Theresa Schumacher and Lukas Bunse and Stefan Pusch and Felix Sahm and Benedikt Wiestler and Jasmin Quandt and Oliver Menn and Matthias Osswald and Iris Oezen and Martina Ott and Melanie Keil and J{\"o}rg Bal{\ss} and Katharina Rauschenbach and Grabowska, {Agnieszka K} and Isabel Vogler and Jan Diekmann and Nico Trautwein and Eichm{\"u}ller, {Stefan B} and J{\"u}rgen Okun and Stefan Stevanovi{\'c} and Riemer, {Angelika B} and Ugur Sahin and Friese, {Manuel A} and Philipp Beckhove and {von Deimling}, Andreas and Wolfgang Wick and Michael Platten",
year = "2014",
month = aug,
day = "21",
doi = "10.1038/nature13387",
language = "English",
volume = "512",
pages = "324--7",
journal = "NATURE",
issn = "0028-0836",
publisher = "NATURE PUBLISHING GROUP",
number = "7514",

}

RIS

TY - JOUR

T1 - A vaccine targeting mutant IDH1 induces antitumour immunity

AU - Schumacher, Theresa

AU - Bunse, Lukas

AU - Pusch, Stefan

AU - Sahm, Felix

AU - Wiestler, Benedikt

AU - Quandt, Jasmin

AU - Menn, Oliver

AU - Osswald, Matthias

AU - Oezen, Iris

AU - Ott, Martina

AU - Keil, Melanie

AU - Balß, Jörg

AU - Rauschenbach, Katharina

AU - Grabowska, Agnieszka K

AU - Vogler, Isabel

AU - Diekmann, Jan

AU - Trautwein, Nico

AU - Eichmüller, Stefan B

AU - Okun, Jürgen

AU - Stevanović, Stefan

AU - Riemer, Angelika B

AU - Sahin, Ugur

AU - Friese, Manuel A

AU - Beckhove, Philipp

AU - von Deimling, Andreas

AU - Wick, Wolfgang

AU - Platten, Michael

PY - 2014/8/21

Y1 - 2014/8/21

N2 - Monoallelic point mutations of isocitrate dehydrogenase type 1 (IDH1) are an early and defining event in the development of a subgroup of gliomas and other types of tumour. They almost uniformly occur in the critical arginine residue (Arg 132) in the catalytic pocket, resulting in a neomorphic enzymatic function, production of the oncometabolite 2-hydroxyglutarate (2-HG), genomic hypermethylation, genetic instability and malignant transformation. More than 70% of diffuse grade II and grade III gliomas carry the most frequent mutation, IDH1(R132H) (ref. 3). From an immunological perspective, IDH1(R132H) represents a potential target for immunotherapy as it is a tumour-specific potential neoantigen with high uniformity and penetrance expressed in all tumour cells. Here we demonstrate that IDH1(R132H) contains an immunogenic epitope suitable for mutation-specific vaccination. Peptides encompassing the mutated region are presented on major histocompatibility complexes (MHC) class II and induce mutation-specific CD4(+) T-helper-1 (TH1) responses. CD4(+) TH1 cells and antibodies spontaneously occurring in patients with IDH1(R132H)-mutated gliomas specifically recognize IDH1(R132H). Peptide vaccination of mice devoid of mouse MHC and transgenic for human MHC class I and II with IDH1(R132H) p123-142 results in an effective MHC class II-restricted mutation-specific antitumour immune response and control of pre-established syngeneic IDH1(R132H)-expressing tumours in a CD4(+) T-cell-dependent manner. As IDH1(R132H) is present in all tumour cells of these slow-growing gliomas, a mutation-specific anti-IDH1(R132H) vaccine may represent a viable novel therapeutic strategy for IDH1(R132H)-mutated tumours.

AB - Monoallelic point mutations of isocitrate dehydrogenase type 1 (IDH1) are an early and defining event in the development of a subgroup of gliomas and other types of tumour. They almost uniformly occur in the critical arginine residue (Arg 132) in the catalytic pocket, resulting in a neomorphic enzymatic function, production of the oncometabolite 2-hydroxyglutarate (2-HG), genomic hypermethylation, genetic instability and malignant transformation. More than 70% of diffuse grade II and grade III gliomas carry the most frequent mutation, IDH1(R132H) (ref. 3). From an immunological perspective, IDH1(R132H) represents a potential target for immunotherapy as it is a tumour-specific potential neoantigen with high uniformity and penetrance expressed in all tumour cells. Here we demonstrate that IDH1(R132H) contains an immunogenic epitope suitable for mutation-specific vaccination. Peptides encompassing the mutated region are presented on major histocompatibility complexes (MHC) class II and induce mutation-specific CD4(+) T-helper-1 (TH1) responses. CD4(+) TH1 cells and antibodies spontaneously occurring in patients with IDH1(R132H)-mutated gliomas specifically recognize IDH1(R132H). Peptide vaccination of mice devoid of mouse MHC and transgenic for human MHC class I and II with IDH1(R132H) p123-142 results in an effective MHC class II-restricted mutation-specific antitumour immune response and control of pre-established syngeneic IDH1(R132H)-expressing tumours in a CD4(+) T-cell-dependent manner. As IDH1(R132H) is present in all tumour cells of these slow-growing gliomas, a mutation-specific anti-IDH1(R132H) vaccine may represent a viable novel therapeutic strategy for IDH1(R132H)-mutated tumours.

KW - Animals

KW - Antibody Specificity

KW - Antigens, Neoplasm

KW - Cancer Vaccines

KW - Female

KW - Glioma

KW - Histocompatibility Antigens Class II

KW - Humans

KW - Immunity, Humoral

KW - Immunotherapy

KW - Isocitrate Dehydrogenase

KW - Male

KW - Mice

KW - Mutant Proteins

KW - Mutation

KW - T-Lymphocytes, Helper-Inducer

KW - Xenograft Model Antitumor Assays

U2 - 10.1038/nature13387

DO - 10.1038/nature13387

M3 - SCORING: Journal article

C2 - 25043048

VL - 512

SP - 324

EP - 327

JO - NATURE

JF - NATURE

SN - 0028-0836

IS - 7514

ER -